TALK CANCELED – Unfortunately Sebastian cannot make it on October 17th. We are trying to postpone the talk – stay tuned for updates…
‘Wenn du Tore schießen möchtest, musst du an der richtigen Stelle stehen’ (if you want to score goals you have to be in the right spot) – that’s what children get taught by their football trainers. If you want to be ‘the fox in the box’ positioning is very important.
This is also true for RNAs. Many mRNAs exhibit a specific sub-cellular localization allowing localized production of proteins. This is of importance in many biological settings: e.g. it equips synapses with a unique proteome, allows directed cell migration, and determines the body axes during early embryonic development.
In mammalian neurons, the asymmetric distribution of mRNAs and local protein synthesis is required for essential processes as cell polarization, migration and synaptic plasticity underlying long-term memory formation. However, the essential components driving cytoplasmic mRNA transport in neurons and mammalian cells are not known.
Mark your calendars: On October 17th at 2p.m. in H53, Sebastian Maurer from the Centre for Genomic regulation (CRG) in Barcelona, Spain, will report the first reconstitution of a mammalian mRNA transport system. His studies reveal that the tumour suppressor adenomatous polyposis coli (APC) forms stable complexes with the axonally localised b-actin and b2B-tubulin mRNAs which are linked to a heterotrimeric kinesin-2 via the cargo adaptor KAP3. APC activates kinesin-2 and both proteins are sufficient to drive specific transport of defined mRNA packages. Guanine-rich sequences located in 3’UTRs of axonal mRNAs increase transport efficiency and balance the access of different mRNAs to the transport system. These findings establish for the first time a minimal set of proteins capable of driving kinesin-based, mammalian mRNA transport.
Last year, the PhD students of the International Giessen Graduate Centre for the Life Sciences (GGL) invited me to to deliver a keynote lecture during the annual conference. To sum up the event: I had a blast! On the one hand, it was great to return to my Alma Mater – the Justus-Liebig-Universität Giessen – for a scientifically very diverse and exciting meeting covering ten interdisciplinary research sections. On the other hand, I could catch up with old friends and colleagues many of whom I am still collaborating with.
This year, a speaker invited to deliver a keynote lecture at the conference unfortunately had to cancel on short notice. I was lucky enough to be asked to step in and present some of our recent data at the 2019 GGL conference on September 4th. Needless to say, that after the great experience last year, I agreed immediatly. And again, I very much enjoyed the conference and the scientific discussions. It was great to see the enthusiasm of the GGL students and to listen to their talks on very diverse and exciting topics.
I would like to thank the students of the ‘Protein and Nucleic Acid Interactions’ section of the GGL (and in particluar Christina Pfafenrot) very much for hosting me and the entire GGL team for the hospitality!
Get motivation letters ready! Registration for the EMBO Practical Course on Measuring Translational Dynamics by Ribosome Profiling is now open. The application deadline is Febraury 9th 2020.
We are thrilled to have a great line-up of speakers and tutors including Nicholas Ingolia (University of California, Berkeley, USA), Rachel Green (Johns Hopkins University School of Medicine, Baltimore, USA), Thomas Preiss (The Australian National University, Canberra, AU), Anne Willis (University of Cambridge, UK), Marina Rodnina (Max Planck Institute for Biophysical Chemistry, Göttingen, DE), Gerben Menschaert (BIOBIX, University of Ghent, BE), and Vladimir Benes (EMBL Heidelberg). During the course, we aim to provide both insight into the theoretical background of ribosome profiling as well as practical sessions with hands-on experimentation and computational training on how to perform ribosome profiling experiments and to analyze the resulting data. We are very much looking forward to your application and to meeting you at the Advanced Training Centre at EMBL Heidelberg in May!
In a collaborative effort spearheaded by the Ahrends lab at the ISAS (Leibniz-Institut für Analytische Wissenschaften) in Dortmund, we established a targeted proteomics approach aimed at analyzing components of the Unfolded Protein Response (UPR), an adaptive signal transduction pathway triggered by the accumulation of unfolded proteins in the endoplasmic reticulum. The UPR comprises an important cellular stress response that aims at re-instating cellular homoeostasis and it plays a key role in a variety of disorders (including diabetes, neurodegenerative disorders, and inflammatory processes). It has also emerged as an attractive target for therapeutic intervention in cancer due to its implication in tumor progression, malignancy and resistance to therapy. The newly developed high-resolution targeted proteomics strategy combines high specificity and sensitivity, allowing the accurate quantification of UPR proteins down to the lower attomol range in a straightforward way without any prior enrichment or fractionation approaches. This has allowed us to determine cellular protein copy numbers of UPR receptors, transducers and effectors, yielding novel insights into an important cellular stress response pathway.
Read the full manuscript at Scientific Reports: Nguyen et al. A sensitive and simple targeted proteomics approach to quantify transcription factor and membrane proteins of the unfolded protein response pathway in glioblastoma cells.
The 24th annual meeting of the RNA Society took place from June 11th to 16th in the beautiful city of Krakow, Poland. It was a scientifically very stimulating conference with great talks on virtually all aspects of RNA biology. I am very happy that our abstract on how Drosophila Sister-of-Sex-lethal antagonizes Sex-lethal auto-regulatory feedback to reinforce a male-specific gene expression pattern was selected for a talk.
The conference also was the perfect opportunity to catch up with colleagues many of which have become close friends over the years – the RNA society truly has become my scientific family!
An EMBO practical course on Measuring Translation Dynamics by Ribosome Profiling is coming up in May 2020. Fantastic speakers are supporting the course including Nicholas Ingolia (University of California, Berkeley, USA), Rachel Green (Johns Hopkins University School of Medicine, Baltimore, USA), Thomas Preiss (The Australian National University, Canberra, AU), Anne Willis (University of Cambridge, UK), Marina Rodnina (Max Planck Institute for Biophysical Chemistry, Göttingen, DE), and Gerben Menschaert (BIOBIX, University of Ghent, BE). The Couse is organized by Sebastian Leidel, Pavel Baranov and Jan Medenbach and will include numerous lectures as well as hands-on training on how to perform ribosome profiling experiments and how to analyze the data. More information will be available soon on the EMBL courses website.
We could successfully extend funding of the Collaborative Research Centre 960 (SFB960) ‘RNP biogenesis: assembly of ribosomal and non-ribosomal RNPs and control of their function’. To continue our ambitious research programs, we are now seeking highly motivated PhD students. We offer a highly competitive research environment and exciting research projects. For more information click here.
Mutations that alter the activity of RNA-binding proteins or their abundance have been implicated in numerous diseases such as neurodegenerative disorders and various types of cancer. This highlights the importance of RBP proteostasis and the necessity to tightly control the expression levels and activities of RBPs. In many cases, RBPs engage in an auto-regulatory feedback by directly binding to and influencing the fate of their own mRNAs, exerting control over their own expression.
Together with our colleagues Michaela Müller-McNicoll from the Institute of Cell Biology and Neuroscience at the Goethe University Frankfurt, Oliver Rossbach from the Institute of Biochemistry at the Justus-Liebig-University Giessen, and Jingyi Hiu at the State Key Laboratory of Molecular Biology (CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology), we have reviewed RBP-mediated autogenous feedback regulation in eukaryotic organisms. For this feedback control, RBPs employ a variety of mechanisms operating at all levels of post-transcriptional regulation of gene expression to either to maintain protein abundance within a physiological range (exerting negative feedback) or to enforce and stabilize cell fate decisions through generation of binary, genetic on/off switches.
The article has just been published in the Journal of Molecular Cell Biology – click here to read the full version.
Good news: the SFB 960 ‘RNP biogenesis: assembly of ribosomes and non-ribosomal RNPs and control of their function’ has been granted another funding period. We are grateful for the generous support by the Deutsche Forschungsgemeinschaft (DFG) that will allow us and our colleagues to continue and extend our scientific programs and to ensure further top-level education of PhD students within the Graduate Research Academy RNA Biology. We want to thank all reviewers that were involved in the selection process and we are looking forward to another four years of exciting science!
A news article on this topic can also be found on the homepage of the University of Regensburg (in German): DFG verlängert Regensburger Sonderforschungsbereich zur Ribosomen-Entstehung
New manuscript published – RhoA regulates translation of the Nogo-A decoy SPARC in white matter-invading glioblastomas
A collaborative effort lead by Björn Tews and supported by the research consortium ‘Systems Biology of the Unfolded Protein Response in Glioma’ (SUPR-G, generously funded by the BMBF in the framework of the e:med initiative) has resulted in a recent publication in Acta Neuropathologica that demonstrates a function of the peptide SPARC in migration and infiltrative growth of glioblastoma cells. SPARC production and secretion is enhanced via regulation of the UPR sensor IRE1 via AKT. SPARC secretion then prevents Nogo-A from inhibiting migration via RhoA. Advanced ultramicroscopy in undissected mouse brains reveals that gliomas require SPARC for invading into white matter structures and its depletion reduces tumor dissemination which significantly prolongs survival and improves response to cytostatic therapy. The discovery of a novel RhoA-IRE1 axis now provides a druggable target for interfering with SPARC production and underscores its therapeutic value. The full publiation can be accessed here.
Mark your calendars! On May 10th at 10a.m. in room VKL 5.1.31, Benedikt Beckmann will talk about novel methods to study RNA-protein interactions during bacterial infection (click here for the advert). Benedikt is a group leader at the Integrated Research Institute (IRI) for the Life Sciences in Berlin, an institute shared between the Humboldt University Berlin, the Charité University Clinic and the Max-Delbrück-Center for Molecular Medicine.
His research focuses on RNA-protein interactions in host cells during infection by pathogenic bacteria which he studies by employing classical molecular biology methods in combination with systems biology approaches and bioinformatics. Using Salmonella typhimurium as a model system, he investigates whether bacterial-derived non-coding RNAs and RNA-binding proteins can directly manipulate host cell gene expression on a post-transcriptional level e.g. to manipulate the immune repsponse of the host.
Recently, Bene established a novel methodological approach to generate RNA interactomes by employing organic extraction for the purification of UV cross-linked ribonucleoproteins (PTex). Previous methods relied on oligo-dT oligonucleotides to capture cross-linked RNPs by hybridization to the poly(A)-tail, limiting their applicability to eukaryotic organisms. Furthermore, Bene will talk about a recently developed machine learning-based tool for the de novo prediction of RNA-binding proteins across a wide variety of species (TriPepSVM).
New manuscript published – Purification of cross-linked RNA-protein complexes by phenol-toluol extraction (PTex)
We are happy that the collaborative effort spearheaded by Benedikt Beckmann at the Integrated Research Institute (IRI) for the Life Sciences has now resulted in a publication. We have described the approach earlier (see here) which, in a nutshell, allows the purification of cross-linked ribonucleoproteins by a series of organic extractions. Access the full article here at Nature Communications.
On February 14th and 15th, the second Regensburg – Canberra Symposium on RNP Biology took place at the John Curtin School of Medical Research at the Australian National University (ANU) in Canberra with the aim to further strengthen our collaborations and to pave the way for establishment of an international PhD program. It was great to meet down under and to hear about the exciting research on RNA biology at the ANU.
I would like to thank our colleagues in Canberra very much for organization of this wonderful meeting and for their generous hospitality.